Conformation of DNA Modified by Monofunctional Ru(II) Arene Complexes: Recognition by DNA Binding Proteins and Repair. Relationship to Cytotoxicity

SummaryWe analyzed DNA duplexes modified at central guanine residues by monofunctional Ru(II) arene complexes [(η6-arene)Ru(II)(en)(Cl)]+ (arene = tetrahydroanthracene or p-cymene, Ru-THA or Ru-CYM, respectively). These two complexes were chosen as representatives of two different classes of Ru(II) arene compounds for which initial studies revealed different binding modes: one that may involve DNA intercalation (tricyclic-ring Ru-THA) and the other (mono-ring Ru-CYM) that may not. Ru-THA is ∼20 times more toxic to cancer cells than Ru-CYM. The adducts of Ru-THA and Ru-CYM have contrasting effects on the conformation, thermodynamic stability, and polymerization of DNA in vitro. In addition, the adducts of Ru-CYM are removed from DNA more efficiently than those of Ru-THA. Interestingly, the mammalian nucleotide excision repair system has low efficiency for excision of ruthenium adducts compared to cisplatin intrastrand crosslinks